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The Journal of Infection Jun 2024The clinical relevance of Mycobacterium malmoense isolation from pulmonary specimens has been considered high compared with other non-tuberculous mycobacteria. In this... (Review)
Review
INTRODUCTION
The clinical relevance of Mycobacterium malmoense isolation from pulmonary specimens has been considered high compared with other non-tuberculous mycobacteria. In this study, we aimed to analyse all published clinical data of patients with M. malmoense isolation to investigate the clinical spectrum, relevance, and outcomes of infections with this uncommon mycobacterium.
METHODS
A systematic review of PubMed, Web of Science, Embase, and Scopus was performed to identify all clinical data about M. malmoense. Random effects meta-analyses of proportions were calculated for clinical relevance, treatment success, and mortality, as well as for other clinical characteristics. A logistic regression analysis, investigating predictors of mortality, as well as Kaplan-Meier survival analyses, were performed.
RESULTS
One hundred and eighty eight patients with individual data from 112 articles and 671 patients with pooled data from 12 articles were included in the meta-analyses. Of patients with individual data, pulmonary infection was the most common manifestation (n = 106/188, 56.4%). One third (n = 61/188, 32.4%) suffered from isolated extra-pulmonary and 21/188 (11.2%) from disseminated disease. In 288 patients with pooled data and pulmonary affection, clinical relevance was high with 68% (95% CI 44-85%) of patients fulfilling criteria for clinical disease. Macrolide and rifamycin-containing regimens were associated with improved survival (adjusted OR 0.12, 95% CI 0.03-0.42, p = 0.002, and 0.23, 95% CI 0.04-0.86, p = 0.03, for lethal events, respectively).
CONCLUSION
In this study, we provide a detailed clinical description of M. malmoense infections. The pathogen is of high clinical relevance for the individual patient with more than 2 out of 3 patients having relevant disease and >40% of manifestations being extra-pulmonary or disseminated. Macrolide and rifamycin-containing regimens are associated with improved survival.
PubMed: 38906266
DOI: 10.1016/j.jinf.2024.106203 -
Microbiology Spectrum Jun 2024The continuous advancement of molecular diagnostic techniques, particularly whole-genome sequencing (WGS), has greatly facilitated the early diagnosis of drug-resistant...
The continuous advancement of molecular diagnostic techniques, particularly whole-genome sequencing (WGS), has greatly facilitated the early diagnosis of drug-resistant tuberculosis patients. Nonetheless, the interpretation of results from various types of mutations in drug-resistant-associated genes has become the primary challenge in the field of molecular drug-resistance diagnostics. In this study, our primary objective is to evaluate the diagnosis accuracy of the World Health Organization (WHO) catalog of mutations and five WGS analysis tools (PhyResSE, Mykrobe, TB Profiler, Gen-TB, and SAM-TB) in drug resistance to 10 anti- (MTB) drugs. We utilized the data of WGS collected between 2014 and 2017 in Zhejiang Province, consisting of 110 MTB isolates as detailed in our previous study. Based on phenotypic drug susceptibility testing (DST) results using the proportion method on Löwenstein-Jensen medium with antibiotics, we evaluated the predictive accuracy of genotypic DST obtained by these tools. The results revealed that the WHO catalog of mutations and five WGS analysis tools exhibit robust predictive capabilities concerning resistance to isoniazid, rifampicin, ethambutol, streptomycin, amikacin, kanamycin, and capreomycin. Notably, Mykrobe, SAM-TB, and TB Profiler demonstrate the most accurate predictions for resistance to pyrazinamide, prothionamide, and para-aminosalicylic acid, respectively. These findings are poised to significantly guide and influence future clinical treatment strategies and resistance monitoring protocols.IMPORTANCEWhole-genome sequencing (WGS) has the potential for the early diagnosis of drug-resistant tuberculosis. However, the interpretation of mutations of drug-resistant-associated genes represents a significant challenge as the amount and complexity of WGS data. We evaluated the accuracy of the World Health Organization catalog of mutations and five WGS analysis tools in predicting drug resistance to first-line and second-line anti-TB drugs. Our results offer clinicians guidance on selecting appropriate WGS analysis tools for predicting resistance to specific anti-TB drugs.
PubMed: 38904370
DOI: 10.1128/spectrum.03341-23 -
Frontiers in Cellular and Infection... 2024Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant , particularly those that are carbapenem resistant. CZA resistance in producing PER, a class A...
INTRODUCTION
Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant , particularly those that are carbapenem resistant. CZA resistance in producing PER, a class A extended-spectrum β-lactamase, has been well documented . However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing clinical isolates that were ceftazidime and/or carbapenem non-susceptible.
METHODS
Antimicrobial susceptibility was determined through agar dilution and broth microdilution, while gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics.
RESULTS
Twenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried . One isolate carried but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum β-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of gene restored susceptibility to CZA, ceftolozane/tazobactam and other β-lactamsin the evolved isolate.
DISCUSSION
PER-3-producing ST309 is a successful multidrug-resistant clone with gene implicated in resistance to CZA and other β-lactams.
Topics: Ceftazidime; Pseudomonas aeruginosa; Azabicyclo Compounds; Microbial Sensitivity Tests; Humans; Drug Combinations; beta-Lactamases; Anti-Bacterial Agents; Pseudomonas Infections; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Chile; Whole Genome Sequencing; Mutation
PubMed: 38903939
DOI: 10.3389/fcimb.2024.1410834 -
Journal of Medical Entomology Jun 2024Insects and microorganisms, ubiquitous organisms in the natural world, have developed intricate relationships throughout their evolutionary histories. However, most...
Insects and microorganisms, ubiquitous organisms in the natural world, have developed intricate relationships throughout their evolutionary histories. However, most studies have concentrated on specific time points or life stages, but some limited studies have investigated the dynamics of microbial diversity within insects across life stages. Here, 16S rDNA sequencing technology was used to investigate the gut bacterial community across the life stages of Sarcophaga peregrina (Robineau-Desvoidy) (Diptera: Sarcophagidae). The results revealed that the gut bacterial diversity of S. peregrina varied with life stage and showed similarity in the nearby life stages. Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes were the dominant phyla in S. peregrina. Genera such as Providencia, Ignatzschineria, and Myroides are implicated in potentially pivotal roles during the developmental processes of this flesh fly. Furthermore, the effects of amikacin on the growth and development of S. peregrina were not statistically significant. However, we did observe significant changes at the protein level, which suggests a close association between protein-level alterations and growth and development. Additionally, we speculate that S. peregrina regulates its nutritional status during nonfeeding stages to meet the demands of eclosion. This study represents the first comprehensive examination of the intestinal bacterial composition across various life stages of S. peregrina. Our findings deepen our understanding of the gut microbiota in this flesh fly and lay the groundwork for further exploration into the intricate interactions between microorganisms and insects.
PubMed: 38902886
DOI: 10.1093/jme/tjae071 -
BMC Microbiology Jun 2024In Addis Ababa, Ethiopia, open ditches along innner roads in residential areas serve to convey domestic wastewater and rainwater away from residences. Contamination of...
BACKGROUND
In Addis Ababa, Ethiopia, open ditches along innner roads in residential areas serve to convey domestic wastewater and rainwater away from residences. Contamination of drinking water by wastewater through faulty distribution lines could expose households to waterborne illnesses. This prompted the study to assess the microbiological safety of wastewater and drinking water in Addis Ababa, identify the pathogens therein, and determine their antibiotic resistance patterns.
RESULTS VIBRIO CHOLERAE
O1, mainly Hikojima serotype, was isolated from 23 wastewater and 16 drinking water samples. Similarly, 19 wastewater and 10 drinking water samples yielded Escherichia coli O157:H7. V. cholerae O1 were 100% resistant to the penicillins (Amoxacillin and Ampicillin), and 51-82% were resistant to the cephalosporins. About 44% of the V. cholerae O1 isolates in this study were Extended Spectrum Beta-Lactamase (ESBL) producers. Moreover, 26% were resistant to Meropenem. Peperacillin/Tazobactam was the only effective β-lactam antibiotic against V. cholerae O1. V. cholerae O1 isolates showed 37 different patterns of multiple resistance ranging from a minimum of three to a maximum of ten antimicrobials. Of the E. coli O157:H7 isolates, 71% were ESBL producers. About 96% were resistant to Ampicillin. Amikacin and Gentamicin were very effective against E. coli O157:H7 isolates. The isolates from wastewater and drinking water showed multiple antibiotic resistance against three to eight antibiotic drugs.
CONCLUSIONS
Open ditches for wastewater conveyance along innner roads in residence areas and underground faulty municipal water distribution lines could be possible sources for V. cholerae O1 and E. coli O157:H7 infections to surrounding households and for dissemination of multiple drug resistance in humans and, potentially, the environment.
Topics: Ethiopia; Vibrio cholerae O1; Wastewater; Escherichia coli O157; Anti-Bacterial Agents; Drinking Water; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial; beta-Lactamases; Humans; Water Microbiology
PubMed: 38902619
DOI: 10.1186/s12866-024-03302-8 -
American Journal of Veterinary Research Jun 2024To establish pilot data on the plasma concentrations of SC amikacin at 2 doses in red-eared sliders and evaluate concurrent plasma biochemistry parameters.
Subcutaneous amikacin administration in red-eared sliders (Trachemys scripta elegans) produces prolonged detectable plasma concentrations without biochemistry evidence of impaired renal function.
OBJECTIVE
To establish pilot data on the plasma concentrations of SC amikacin at 2 doses in red-eared sliders and evaluate concurrent plasma biochemistry parameters.
ANIMALS
8 adult red-eared sliders (Trachemys scripta elegans).
METHODS
Amikacin was administered SC at target doses of 5 and 10 mg/kg with a 3-week washout period. Blood samples were collected at 0, 24, 48, 72, and 96 hours postadministration. Plasma amikacin concentrations were quantified using liquid chromatography tandem mass spectrometry. Plasma biochemistry analyses were performed before amikacin administration, 1 week post 5-mg/kg administration, and 1 week post 10-mg/kg administration.
RESULTS
Mean maximum amikacin plasma concentrations were recorded 24 hours after 5-mg/kg and 10-mg/kg dosing and were 17.5 ± 2.32 µg/mL and 23.6 ± 2.92 µg/mL, respectively. Mean plasma concentrations after 5-mg/kg dosing steadily decreased to 9.1 ± 0.92 µg/mL by 96 hours postadministration. Amikacin remained detectable in all plasma samples 3 weeks post 5-mg/kg dosing with a mean plasma concentration of 1.04 ± 0.22 µg/mL. Mean plasma concentrations after 10-mg/kg dosing did not decrease over the 96-hour study period. There were no clinically relevant changes in biochemistry parameters.
CLINICAL RELEVANCE
Amikacin persists at detectable plasma levels for at least 3 weeks after SC administration of a 5-mg/kg dose in red-eared sliders, which has not previously been reported in any species. No biochemistry changes consistent with renal toxicity occurred after either dose. Use caution with repeated amikacin dosing in this species until further studies can better characterize cumulative amikacin pharmacokinetics and toxic threshold.
PubMed: 38901454
DOI: 10.2460/ajvr.24.03.0088 -
Cureus May 2024Background and objective Urinary tract infections (UTIs) are a common infectious disease affecting people of various ages and genders and are prevalent in different...
The Prevalence of Multidrug-Resistant Uropathogenic Bacterial Profile With Antibiotic Susceptibility Patterns Among the Community and Hospitalized Patients During COVID Waves.
Background and objective Urinary tract infections (UTIs) are a common infectious disease affecting people of various ages and genders and are prevalent in different geographical locations. However, the way Gram-positive and Gram-negative (UTI) germs react to antibiotic treatment varies significantly. The coronavirus disease 2019 (COVID-19) pandemic has increased the frequency of secondary bacterial superinfection, leading to a spike in ongoing recommendations for antibiotic treatment, both therapeutic and preventative. In this study, we aimed to assess uropathogenic bacterial resistance and shed light on how COVID-19 epidemic waves influence the evolution of bacterial resistance. Materials and methods A cross-sectional study was conducted, assessing the different isolates of the uropathogen in all COVID-19 waves by using convenience sampling from August 2020 till the end of 2023. The VITEK-2 compact system employing industry-standard bacteriological tests to identify the bacteria and confirm their antibiotic susceptibility was utilized. Results Of the total 3877 patients, 381 (9.8%) and 3483 (89.8%) had positive and negative microbial growth, respectively. Of the 381 (9.8%) positive cases, 130 (34%) were male and 251 (65%) were female; 138 (43.3%) patients in the age range of 15-40 years developed sporadic UTIs attributed to Gram-negative bacteria. Alternatively, patients over 40 years had the highest prevalence rate (n = 180, 56.6%). The most common strains of Gram-negative and Gram-positive bacteria were and with278 (88.8%) and 13 (20.9%) cases respectively. People with Gram-negative bacteria who were not hospitalized were very resistant to trimethoprim/sulfamethoxazole (n = 219, 69.1%), cefotaxime (n = 193, 60.9%), ampicillin (n = 192, 60.6%), and amoxicillin/clavulanic acid (176, 55.5%). While high sensitivity to meropenem (n = 14, 4.4%) and imipenem (n = 13, 4.1%) was observed, hospitalized individuals had higher levels of resistance and great sensitivity to the same antibiotics. S. . were commonly present. Hospitalized patients were less sensitive to benzylpenicillin, ampicillin, and oxacillin, and there was a big rise in resistance to cefoxitin in the community. Conclusions In this study, Gram-negative germs among females were predominantly observed with extremely high multi-drug resistance (MDR). The most effective antibiotics against Gram-positive germs included linezolid, vancomycin, and nitrofurantin, while those against Gram-negative bacteria were meropenem and amikacin. Clinicians should be regularly updated and informed about antibiotic selection through routine monitoring of uropathogenic bacteria's susceptibility. Moreover, we recommend changes to the local antibiotic policy regarding the selection of UTIs; further multicentric and high-volume studies are required to gain deeper insights into the topic.
PubMed: 38894805
DOI: 10.7759/cureus.60613 -
Equine Veterinary Journal Jun 2024Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions...
BACKGROUND
Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions of the distal limb.
OBJECTIVES
The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin.
STUDY DESIGN
Randomised cross-over in vivo experiment.
METHODS
Six horses underwent IVRLP with 0.1 mg/kg morphine sulphate diluted to 60 mL using 0.9% NaCl (M group) or combined with 2 g amikacin and 0.9% NaCl (MA group) with a 2-week washout period between treatments. Synovial fluid was collected from the radiocarpal joint (RCJ) at 10, 20, 30, 120, 240, 480, 720 and 1440 min after IVRLP. The tourniquet was removed after the 30-min sample was collected. Synovial concentrations of morphine and major metabolites were measured using liquid chromatography-tandem mass spectrometry. Amikacin concentrations were quantified by a fluorescence polarisation immunoassay.
RESULTS
Measurable concentrations of morphine were apparent in the RCJ of all horses. Median C of morphine in the M group was 4753.1 (2115.7-14 934.5) ng/mL and 4477 (3434.3-7363) ng/mL in the MA group (p = 0.5). Median C of synovial amikacin was 322.6 (157.5-1371.6 μg/mL).
MAIN LIMITATIONS
Limitations include small sample size. Investigators were not blinded to the treatments and a third treatment group where amikacin alone was administered via IVRLP to the study population was not included.
CONCLUSIONS
IVRLP using morphine is a feasible technique and synovial morphine concentrations were measurable following IVRLP and were not affected when used concurrently with amikacin. Administration of morphine via IVRLP may be beneficial as an analgesic technique for orthopaedic conditions of the distal limb while limiting potential serious systemic side-effects.
PubMed: 38887833
DOI: 10.1111/evj.14114 -
Frontiers in Microbiology 2024Non-Tuberculous mycobacteria (NTM) are opportunistic environmental bacteria. Globally, NTM incidence is increasing and modeling suggests that, without new interventions,... (Review)
Review
Non-Tuberculous mycobacteria (NTM) are opportunistic environmental bacteria. Globally, NTM incidence is increasing and modeling suggests that, without new interventions, numbers will continue to rise. Effective treatments for NTM infections remain suboptimal. Standard therapy for complex, the most commonly isolated NTM, requires a 3-drug regime taken for approximately 18 months, with rates of culture conversion reported between 45 and 70%, and high rates of relapse or reinfection at up to 60%. New therapeutic options for NTM treatment are urgently required. A survey of ongoing clinical trials for new NTM therapy listed on ClinicalTrials.Gov using the terms '', '', '', 'Non tuberculous Mycobacteria' and 'Nontuberculous Mycobacteria' and a selection criterion of interventional studies using antibiotics demonstrates that most trials involve dose and combination therapy of the guideline based therapy or including one or more of; Amikacin, Clofazimine, Azithromycin and the anti-TB drugs Bedaquiline and Linezolid. The propensity of NTMs to form biofilms, their unique cell wall and expression of both acquired and intrinsic resistance, are all hampering the development of new anti-NTM therapy. Increased investment in developing targeted treatments, specifically for NTM infections is urgently required.
PubMed: 38887711
DOI: 10.3389/fmicb.2024.1394220 -
Journal of Clinical Laboratory Analysis May 2024The global spread of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) poses a significant concern. Acquisition of...
BACKGROUND
The global spread of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) poses a significant concern. Acquisition of antimicrobial resistance genes leads to resistance against several antibiotics, limiting treatment options. We aimed to study ESBL-producing and CRE transmission in clinical settings.
METHODS
From clinical samples, 227 ESBL-producing and CRE isolates were obtained. The isolates were cultured on bacterial media and confirmed by VITEK 2. Antibiograms were tested against several antibiotics using VITEK 2. The acquired resistance genes were identified by PCR.
RESULTS
Of the 227 clinical isolates, 145 (63.8%) were Klebsiella pneumoniae and 82 (36.1%) were Escherichia coli; 76 (33.4%) isolates were detected in urine, 57 (25.1%) in pus swabs, and 53 (23.3%) in blood samples. A total of 58 (70.7%) ESBL-producing E. coli were resistant to beta-lactams, except for carbapenems, and 17.2% were amikacin-resistant; 29.2% of E. coli isolates were resistant to carbapenems. A total of 106 (73.1%) ESBL-producing K. pneumoniae were resistant to all beta-lactams, except for carbapenems, and 66.9% to ciprofloxacin; 38 (26.2%) K. pneumoniae were resistant to carbapenems. Colistin emerged as the most effective antibiotic against both bacterial types. Twelve (20.6%) E. coli isolates were positive for bla, 11 (18.9%) for bla, and 8 (33.3%) for bla. Forty-six (52.3%) K. pneumoniae isolates had bla, 27 (18.6%) bla, and 26 (68.4%) bla.
CONCLUSION
This study found a high prevalence of drug-resistant ESBL-producing and CRE, highlighting the need for targeted antibiotic use to combat resistance.
Topics: Klebsiella pneumoniae; Humans; Escherichia coli; beta-Lactamases; Microbial Sensitivity Tests; Anti-Bacterial Agents; Carbapenems; Female; Male; Middle Aged; Adult; Aged; Carbapenem-Resistant Enterobacteriaceae; Adolescent; Young Adult; Escherichia coli Infections; Klebsiella Infections; Child; Child, Preschool; Drug Resistance, Bacterial
PubMed: 38884333
DOI: 10.1002/jcla.25081